The outer capsid protein VP4 of porcine rotavirus OSU was chosen as a model to study the immunogenicity of this protein expressed by an adenovirus vector. The ability of adenovirus to be administered orally makes the potential use of adenovirus vectors for vaccine production particularly attractive. In addition, live adenovirus vaccines have already been shown to be safe in humans when administered orally in enteric coated capsules. The full-length cDNA of the VP4 of the porcine rotavirus OSU strain was cloned into adenovirus type 5 at a location downstream of the E3 promoter. In this viable recombinant the rotavirus VP4 sequence was substituted for sequences in the adenovirus E3 region. The plaque- purified recombinant (Ad5-OSU VP4), expressed an antigenically authentic VP4 protein as determined by immunoprecipitation. The 84 kDa protein had the same electrophoretic mobility as the native VP4 of OSU rotavirus grown in MA104 cells. Preliminary results from a study in which cotton rats were infected intranasally with live Ad5-OSU VP4 indicated that the animals developed a low level of neutralizing antibodies to the OSU porcine rotavirus.